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WO2002010424A1 - Procede de preparation d'acetal d'allysine - Google Patents

Procede de preparation d'acetal d'allysine Download PDF

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Publication number
WO2002010424A1
WO2002010424A1 PCT/EP2001/007387 EP0107387W WO0210424A1 WO 2002010424 A1 WO2002010424 A1 WO 2002010424A1 EP 0107387 W EP0107387 W EP 0107387W WO 0210424 A1 WO0210424 A1 WO 0210424A1
Authority
WO
WIPO (PCT)
Prior art keywords
preparation
process according
cell catalyst
total cell
specific
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2001/007387
Other languages
English (en)
Inventor
Hans-Peter Krimmer
Oliver May
Ingo Klement
Karlheinz Drauz
Dietmar Reichert
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Evonik Operations GmbH
Original Assignee
Degussa GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Degussa GmbH filed Critical Degussa GmbH
Priority to AU2001269104A priority Critical patent/AU2001269104A1/en
Priority to EP01947418A priority patent/EP1305441A1/fr
Publication of WO2002010424A1 publication Critical patent/WO2002010424A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/04—Alpha- or beta- amino acids

Definitions

  • the present invention is directed towards the preparation of compounds of the general formula (I)
  • Such compounds are prepared in particular by means of an enzymatic process from hydantoins of the general formula (II)
  • the object of the present invention was to provide a further enzymatic process for the preparation of the desired compounds.
  • that process was to be more simple to carry out and hence more suitable for use in a large-scale process.
  • R represents (C ⁇ -C 8 )- alkyl, (C 2 -C 4 ) -alkylenyl, preferably ethylenyl, (C 6 -C ⁇ 8 )- aryl, (C 7 -C ⁇ 9 ) -aralkyl, (C ⁇ -C 8 ) -acyl, wherein the latter are subjected to a reaction with hydantoinases and D- or L- specific carbamoylases, as well as to a spontaneous and/or enzyme-catalysed in situ racemisation, and wherein the enzymes involved may be used in free form, in immobilised form or in a form enclosed in cells, the desired compounds such as (I) are obtained in a manner that is surprising for a large-scale process but advantageous.
  • reaction sequence according to the invention has hitherto not been applied in the prior art to the present compounds. It is therefore to be regarded as surprising that the labile acetal protecting group is stable under the reaction conditions and allysine acetal having an optical purity >99%ee can be generated in a very high yield from 100% of the hydantoin in an overall yield >85%.
  • the process according to the invention may be carried out partially enzymatically or completely enzymatically.
  • a so-called whole cell catalyst which has a cloned gene coding for a hydantoin racemase, a hydantoinase and an L- or D- specific carbamoylase.
  • Such organisms are known in principle from US 60/157427 (seq. 4/hydantoinase, 5/hydantoin racemase, 6/carbamoylase) or US 09/407062 (seq. 1/hydantoinase, 2/hydantoin racemase,
  • the total cell catalyst may be any suitable expression system that comes into consideration for that purpose to those skilled in the art. Special preference is given, however, to the use of a recombinant bacterium, preferably E. coli, for the purpose.
  • Advantageous E. coli strains are: JM109, NM 522, JM105, RR1, DH5 ⁇ , TOP 10 " or HB101.
  • the substrate (II) is brought into contact with the enzymes in a suitable solvent, preferably water, at an optimum pH value for hydantoinase and carbamoylase of approximately from 5.5 to 8.5, preferably from 6.5 to 8, and at an optimum temperature for the enzyme activity of approximately from 20°C to 40°C, preferably from 25°C to 35°C.
  • a suitable solvent preferably water
  • metal salts that have a positive effect on the enzyme activities, such as CoCl 2 or MgCl 2 , MnCl 2 , etc.
  • the hydantoin that remains can be racemised enzymatically in situ and is thus available for cleavage into the amino acid again. For reasons of time, therefore, 5 enzymatic racemisation that proceeds simultaneously with the conversion of the hydantoin to the amino acid is preferably strived for. All the hydantoin can thus be converted into the amino acid in one step. As has been stated, that may be effected using enzymes that are
  • the process according to the invention may be carried out in sequential reaction batches or continuously in a so-
  • the invention relates to the use of the acetals prepared according to the invention in a 20 synthesis for the preparation of active ingredients, especially pharmaceuticals, having biological activity.
  • (C ⁇ C 8 ) -Alkyl is to be regarded as being methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl or octyl, including all 25 their isomers formed due to different positions of the double bond.
  • (C ⁇ -C 8 ) -Alkylenyl is to be understood as meaning alkyl bridges having from 2 to 8 carbon atoms, the substituents being in the 1- and n-position, such as, for example, 30 ethylenyl, propylenyl, etc..
  • a (C 6 -Ci 8 ) -aryl radical is to be understood as being an aromatic radical having from 6 to 18 carbon atoms. It includes in particular compounds such as phenyl, naphthyl, anthryl, phenanthryl, biphenyl radicals.
  • a (C7-C19) -aralkyl radical is a (C 6 -C 18 ) -aryl radical bonded to the molecule via a (C ⁇ C 8 ) -alkyl radical.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

L'invention concerne la préparation de composés correspondant à la formule (I) à partir d'hydantoïnes correspondants au moyen d'un procédé enzymatique. Le composé L est de préférence formé.
PCT/EP2001/007387 2000-07-28 2001-06-28 Procede de preparation d'acetal d'allysine Ceased WO2002010424A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2001269104A AU2001269104A1 (en) 2000-07-28 2001-06-28 Process for the preparation of allysine acetal
EP01947418A EP1305441A1 (fr) 2000-07-28 2001-06-28 Procede de preparation d'acetal d'allysine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10037115.9 2000-07-28
DE10037115A DE10037115A1 (de) 2000-07-28 2000-07-28 Verfahren zur fermentativen Herstellung von L-Allysinacetal

Publications (1)

Publication Number Publication Date
WO2002010424A1 true WO2002010424A1 (fr) 2002-02-07

Family

ID=7650736

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/007387 Ceased WO2002010424A1 (fr) 2000-07-28 2001-06-28 Procede de preparation d'acetal d'allysine

Country Status (7)

Country Link
US (1) US6825014B2 (fr)
EP (1) EP1305441A1 (fr)
AR (1) AR029840A1 (fr)
AU (1) AU2001269104A1 (fr)
DE (1) DE10037115A1 (fr)
TW (1) TWI272309B (fr)
WO (1) WO2002010424A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007084545A1 (fr) * 2006-01-18 2007-07-26 Dow Global Technologies Inc. Procédé de synthèse d'acides aminés

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0625571A2 (fr) * 1993-05-19 1994-11-23 Degussa Aktiengesellschaft Microorganismes, leurs utilisation et méthode de production d'acides amines L-alpha
JPH11206397A (ja) * 1998-01-29 1999-08-03 Dai Ichi Pure Chem Co Ltd 光学活性α−アミノアジピン酸−γ−セミアルデヒドエチレンアセタールの製造方法
WO2001023582A1 (fr) * 1999-09-28 2001-04-05 Degussa Ag Catalyseur cellule totale renfermant une hydantoinase, une racemase et une carbamoylase
WO2001023535A2 (fr) * 1999-09-27 2001-04-05 Degussa Ag Hydantoïne-racémase

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6524837B1 (en) 1999-03-29 2003-02-25 California Institute Of Technology Hydantoinase variants with improved properties and their use for the production of amino acids

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0625571A2 (fr) * 1993-05-19 1994-11-23 Degussa Aktiengesellschaft Microorganismes, leurs utilisation et méthode de production d'acides amines L-alpha
JPH11206397A (ja) * 1998-01-29 1999-08-03 Dai Ichi Pure Chem Co Ltd 光学活性α−アミノアジピン酸−γ−セミアルデヒドエチレンアセタールの製造方法
WO2001023535A2 (fr) * 1999-09-27 2001-04-05 Degussa Ag Hydantoïne-racémase
WO2001023582A1 (fr) * 1999-09-28 2001-04-05 Degussa Ag Catalyseur cellule totale renfermant une hydantoinase, une racemase et une carbamoylase

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BOMMARIUS A S ET AL: "MEMBRANE BIOREACTORS FOR THE PRODUCTION OF ENANTIOMERICALLY PURE ALPHA-AMINO ACIDS", CHIRALITY, WILEY-LISS, NEW YORK, US, PAGE(S) 371-397, ISSN: 0899-0042, XP000991099 *
MAY OLIVER ET AL: "Inverting enantioselectivity by directed evolution of hydantoinase for improved production of L-methionine", NATURE BIOTECHNOLOGY, NATURE PUBLISHING, US, vol. 18, no. 3, March 2000 (2000-03-01), pages 317 - 320, XP002154849, ISSN: 1087-0156 *
WOHLFAHRT G ET AL: "IMMOBILIZATION OF HYDANTOIN CLEAVING ENZYMES", DECHEMA BIOTECHNOLOGY CONFERENCES, WEINHEIM, DE, vol. 5, no. PART A, 1992, pages 45 - 48, XP000991533, ISSN: 0934-3792 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007084545A1 (fr) * 2006-01-18 2007-07-26 Dow Global Technologies Inc. Procédé de synthèse d'acides aminés

Also Published As

Publication number Publication date
US20020132848A1 (en) 2002-09-19
DE10037115A1 (de) 2002-02-07
US6825014B2 (en) 2004-11-30
AU2001269104A1 (en) 2002-02-13
AR029840A1 (es) 2003-07-16
EP1305441A1 (fr) 2003-05-02
TWI272309B (en) 2007-02-01

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